Assessment of three levels of folic acid on serum folate and plasma homocysteine: a randomised placebo-controlled double-blind dietary intervention trial

Objective: To determine the minimum effective dose of folic acid required to appreciably increase serum folate and to produce a significant reduction in plasma total homocysteine (tHcy). Design: Double-blind, randomised placebo-controlled intervention trial. Setting: Community-based project in a New Zealand city. Subjects: Seventy free living men and women with tHcy greater than or equal to 10 mumol/l. Mean age (range) was 58 (29-90) y. Interventions: Daily consumption over 4 weeks of 20 g breakfast cereal either unfortified (placebo) or fortified with 100, 200 or 300 mug folic acid. Dietary intake was determined by weighed diet records and consumption of commercially fortified products was avoided. Main outcome measures: Plasma tHcy and serum folate concentrations. Results: Average serum folate concentrations (95% CI) increased significantly in the treatment groups relative to the control group by 28(9-51)%, 60(37-87)% and 79(51-114)% for supplementation with 100, 200 and 300 mug folic acid, respectively. A reduction in tHcy was observed, being 16(8-22)%, 12(4-18)% and 17(9-24)% in the three treatment groups, respectively. Conclusions: A regular intake of as little as 100 mug folic acid per day was sufficient to lower tHcy in persons at the upper end of the normal range for tHcy. Low-level fortification may also be appropriate for lowering the risk of neural tube defects given that, when aggregated from all sources, the total intake of folic acid may be sufficiently high to adequately improve the folate status of young women. Funding: The breakfast cereals were supplied and the study partially funded by Kellogg Company.